Diet and Exercise Training Influence Skeletal Muscle Long-Chain acyl-CoA Synthetases

Long-chain acyl-CoA synthetases (ACSL) are implicated as regulators of oxidation and storage of fatty acids within skeletal muscle; however, to what extent diet and exercise alter skeletal muscle ACSL remains poorly understood.

This study aimed to determine the effects of diet and exercise training on skeletal muscle ACSL and to examine relationships between ACSL1 and ACSL6 and fat oxidation and fat storage, respectively.

Male C57BL/6J mice consumed a 60% high-fat diet (HFD) for 12 wk to induce obesity compared with low-fat diet (LFD). At week 4, mice began aerobic exercise (EX-Tr) or remained sedentary (SED) for 8 wk. At week 12, the protein abundance of five known ACSL isoforms and mRNA expression for ACSL1 and ACSL6 were measured in gastrocnemius muscle, as was skeletal muscle lipid content. Fat oxidation was measured using metabolic cage indirect calorimetry at week 10.

Of the five known ACSL isoforms, four were detected at the protein level. HFD resulted in greater, yet nonsignificant, ACSL1 protein abundance (+18%, P = 0.13 vs LFD), greater ACSL6 (+107%, P < 0.01 vs LFD), and no difference in ACSL4 or ACSL5. Exercise training resulted in greater ACSL6 protein abundance in LFD mice (P = 0.05 LFD EX-Tr vs SED), whereas ACSL4 was lower after exercise training compared with sedentary, regardless of diet. Under fasted conditions, skeletal muscle ACSL1 protein abundance was not related to measures of whole-body fat oxidation. Conversely, skeletal muscle ACSL6 protein abundance was positively correlated with intramyocellular lipid content (P < 0.01, r = 0.22).

We present evidence that ACSL isoforms 1, 4, and 6 may undergo regulation by HFD and/or exercise training. We further conclude that increased skeletal muscle ACSL6 may facilitate increased intramyocellular fat storage during HFD-induced obesity.